Objective To establish a cell bank of extrahepatic cholangiocarcinoma (ECC)-derived organoids and investigate the key factors influencing the organoids generation. Methods The tumor samples from patients with portal cholangiocarcinoma (pCCA) and distal cholangiocarcinoma (dCCA) were used to isolate cells, and these cells were cultured using three-dimensional (3D) technique to establish ECC organoids. Histological characteristics of the organoids were evaluated and identified through hematoxylin-eosin (HE) and immunohistochemistry stainings. The success rates of organoids generation from different tumor types were compared. And clinical characteristics of patients between successful and failure culture groups were compared. Results The success rates of organoids establishment from pCCA and dCCA were all low, with 42.4% (14/33), 51.9% (14/27), respectively. The tumor was larger in successful group than that in failure group (P＜0.001); there was no statistical difference in tumor differentiation status, microvascular invasion, and perineural invasion between the two groups. Conclusions The successful rate of ECC-derived organoids establishment is low, and larger tumor has higher successful culture rate.

Heart failure with preserved ejection fraction (HFpEF) displays normal or near-normal left ventricular ejection fraction, diastolic dysfunction, cardiac hypertrophy, and poor exercise capacity. Berberine, an isoquinoline alkaloid, possesses cardiovascular benefits. Adult male mice were assigned to chow or high-fat diet with L-NAME ("two-hit" model) for 15 weeks. Diastolic function was assessed using echocardiography and noninvasive Doppler technique. Myocardial morphology, mitochondrial ultrastructure, and cardiomyocyte mechanical properties were evaluated. Proteomics analysis, autophagic flux, and intracellular Ca²⁺ were also assessed in chow and HFpEF mice. The results show exercise intolerance and cardiac diastolic dysfunction in "two-hit"-induced HFpEF model, in which unfavorable geometric changes such as increased cell size, interstitial fibrosis, and mitochondrial swelling occurred in the myocardium. Diastolic dysfunction was indicated by the elevated E value, mitral E/A ratio, and E/e' ratio, decreased e' value and maximal velocity of re-lengthening (-dL/dt), and prolonged re-lengthening in HFpEF mice. The effects of these processes were alleviated by berberine. Moreover, berberine ameliorated autophagic flux, alleviated Drp1 mitochondrial localization, mitochondrial Ca²⁺ overload and fragmentation, and promoted intracellular Ca²⁺ reuptake into sarcoplasmic reticulum by regulating phospholamban and SERCA2a. Finally, berberine alleviated diastolic dysfunction in "two-hit" diet-induced HFpEF model possibly because of the promotion of autophagic flux, inhibition of mitochondrial fragmentation, and cytosolic Ca²⁺ overload.
Male ; Mice ; Animals ; Heart Failure/drug therapy* ; Stroke Volume/physiology* ; Ventricular Function, Left/physiology* ; Berberine/therapeutic use* ; Disease Models, Animal ; Mitochondrial Dynamics ; Myocardium ; Homeostasis

Objective To study the genetic diversity of germplasm resources for Potentilla discolor.Methods Twelve species of germplasm resources for P.discolor were analyzed by ISSR molecular markers.To make up the systematic diagram of genetic relationship by POPGENE 1.32 software,cluster by UPGMA method,and establish the dendrogram.Results A total of 128 ISSR bands were scored for 12 primers,among which 101 were polymorphic bands.The average percentage of polymorphic bands was 78.91%.Genetic similarity coefficient was changed from 0.179 2 to 0.632 5.By cluster analysis,the geographical distribution is mutually related to the relationship of germplasm resources for P.discolor and it was also showed some of P.discolor from the same region were in the same group which presented the rule of geographical distribution in the tested materials.Conclusion The diversity level of the different germplasm resources for P.discolor higher and the relationship of P.discolor correlates with the geographical location in some way.